(in mg/kg) should be lower in neonates and infants with low albumin because of both decreased protein binding as well as decreased elimination by renal and/or hepatic metabolism. Examples of high ER drugs that are highly protein bound (ie, >70%) with narrowtherapeutic windowsincludealfentanil,...
Such studies have laid the foundation for discovering drugs that selectively disrupt specific ATG8–LIR interactions. Download: Download high-res image (694KB) Download: Download full-size image Figure 2. Structural features of ATG8 family proteins and two examples of LC3 inhibitors. (A) ...
Understanding protein–drug binding mechanisms, and characterizing their thermodynamics and kinetics are fundamental prerequisites to developing effective drug discovery procedures and, indeed, to developing effective drugs. It has been demonstrated that the duration of the pharmacological action1,2,3,4 of ...
This article uses examples to describe general strategies in the development of small molecule antagonists of protein–protein interactions. Two types of antagonists are described: those that bind directly to the 'hot spot'of a protein–protein interface — a region that has a major contribution to...
Recent protein structure predictions based on machine learning tools have delivered surprisingly reliable results for water-soluble and membrane proteins but have limitations for development of drugs that target membrane proteins. Structural transitions of membrane proteins have a central role during ...
Therefore, determining the structures of protein–peptide interactions is valuable for studying their molecular mechanism and thus developing peptide drugs [5, 6]. However, due to the high cost and technical difficulties, only a small portion of protein–peptide complex structures were experimentally ...
and the development of robust and high-throughput-suitable assays for the discovery of novel ligands and drugs targeting these proteins. In principle, the screening of ligands can be performed in whole-cell assays by measuring a downstream signaling event, or in CF assays, which are decoupled fro...
Classification of protein–protein interaction types based on affinity and stability. Stable complex (PDB: 1 F34) Structure of Ascaris pepsin inhibitor-3 bound to Porcine pepsin; Transient Domain-Domain interaction (PDB: 1AY7) Structure of the Ribonuclease SA Complex With Barstar; Transient Domain...
Because the majority of drugs are bound toplasma proteinsor tissuebinding sites, the most commonly cited mechanisms for drug–drug interactions affecting distribution are those that involve protein or tissue binding. Several examples exist in which one drug displaces an object drug through competitive ...
(containing the viral genome) into the cell. In some viruses the sameviral envelope proteinexpresses both of these functions. Examples include influenza virus (HA protein), vesicular stomatitis virus (G protein), andSemliki Forest virus(E protein). Inparamyxoviruses, likeSendai virus, the two ...